Bioequivalence and Bioavailability Forum • Incurred sample reanalysis

Incurred sample reanalysis [Regulatives / Guidelines]

posted by Ohlbe – France, 2013-04-09 16:09 (4436 d 16:36 ago) – Posting: # 10382
Views: 15,840

Dear Srinivas,

❝ Hi Helmut,

Not interested in the opinion of other members of the forum ?

❝ Incurred sample reanalysis has been suggested by USFDA

It is now also required for EMA submission.

❝ 1. When the whole validation has been done based on in vitro samples and when the results of these experiments have been accepted then why ISR again?

Because in vitro samples are not fully representative of the subject samples. They usually do not contain metabolites, and I've never seen overfilled QC samples (two of the possible causes of ISR failure).

❝ 2. When Long Term Matrix Stability of the drug and metabolites are proven taking invitro samples is proven and when the stability of such experiment is accepted then why ISR again?

The long-term stability is not the only issue anyway: back-conversion during sample processing can be of greater concern. And are you sure you know all metabolites ? EMA got trapped in their recommendations on clopidogrel.¹

❝ 3. Even though the ISR samples are reanalysed they are analysed along with CCs and QCs which are invitro again!!!!

So what ? The idea with ISR is to test for the variability of the method when analysing subject samples. Some variability factors affect the subject samples more than the CCs and QCs, which are used as a reference.

❝ 4. What if ISR fails?? probably they have to ascertain the cause and go for the development of the method again?????

First try and find the reason for failure, and see if and how it can be corrected.

Luigi Silvestro, Mihaela Cristina Gheorghe, Isabela Tarcomnicu, Silviu Savu, Simona Rizea Savu, Adriana Iordachescu and Constanta Dulea
Development and validation of an HPLC–MS/MS method to determine clopidogrel in human plasma. Use of incurred samples to test back-conversion
Journal of Chromatography B, 878 (2010) 3134–3142
doi:10.1016/j.jchromb.2010.09.022

For more info on ISR have a look e.g. at:

M. Yadav, P. S. Shrivastav
Incurred sample reanalysis (ISR): a decisive tool in bioanalytical research
Bioanalysis (2011) 3(9), 1007–1024

A. Tan, S. Gagnon-Carignan, Sylvain Lachance et al.
Beyond successful ISR: case-by-case investigations for unmatched reassay results when ISR passed
Bioanalysis (2011) 3(9), 1031–1038

—
Regards
Ohlbe

Complete thread:

Incurred sample reanalysis sarada06884 2013-04-09 12:22 [Regulatives / Guidelines]
- Incurred sample reanalysisOhlbe 2013-04-09 14:09
  - Incurred sample reanalysis The Outlaw Torn 2013-04-10 08:40
    - Clopidogrel Ohlbe 2013-04-10 10:34
      - Clopidogrel The Outlaw Torn 2013-04-10 11:31
        
        Lack of ISR / only 5% ISR in study with 656 samples Helmut 2013-04-22 17:01
        
        Lack of ISR / only 5% ISR in study with 656 samples ElMaestro 2013-04-22 18:56
        
        Lack of ISR / only 5% ISR in study with 656 samples Helmut 2013-04-22 19:35
        
        "Meth" - apologies ElMaestro 2013-04-22 20:03
        
        "Meth" - apologies The Outlaw Torn 2013-04-23 08:27
        
        "Meth" - apologies ElMaestro 2013-04-23 14:29
        
        "ISR" - apologies The Outlaw Torn 2013-04-24 07:44
        
        Repeat use ElMaestro 2013-04-24 11:08
        
        Repeat use Ohlbe 2013-04-24 11:41
        
        Repeat use ElMaestro 2013-04-24 13:45
        
        "ISR" – resolved Helmut 2013-09-20 21:50
        
        "ISR" – resolved Dr_Dan 2013-09-22 16:56
        
        Lack of ISR / only 5% ISR in study with 656 samples ElMaestro 2013-04-23 23:31
        
        Some more stuff Helmut 2013-04-24 02:08
        Lack of ISR / only 5% ISR in study with 656 samples nobody 2014-10-23 10:06